Daily Ards Research Analysis

BACKGROUND: Respiratory distress syndrome (RDS), or hyaline membrane disease, is a common condition in preterm infants (< 37 weeks' gestation) and a leading cause of neonatal morbidity and mortality. The risk is highest in extremely preterm (< 28 weeks) and very preterm (28 to < 31 weeks) infants due to immature lung and cardiovascular development. RDS results from a deficiency or dysfunction of pulmonary surfactant, which lines the alveoli to reduce surface tension, prevent atelectasis, and protect the lungs. Surfactant is primarily composed of dipalmitoylphosphatidylcholine (DPPC), other phospholipids, and four proteins that support its function, recycling, and innate lung defense. Surfactant replacement therapy improves lung compliance, reduces the need for ventilator support, and decreases the risk of pneumothorax, death, and the combined outcome of death or bronchopulmonary dysplasia. Its widespread use has substantially improved survival among preterm infants without increasing long-term neurological or developmental disability. Various surfactant preparations, including animal-derived, synthetic, and protein or peptide-containing formulations have been evaluated. Surfactant can be administered prophylactically immediately after birth or selectively once RDS develops. Both strategies are effective, with theoretical advantages and disadvantages. Prophylactic surfactant may prevent respiratory insufficiency, reduce the need for ventilator support, and distribute surfactant more evenly in fluid-filled lungs, lowering the risk of lung injury. Selective treatment targets only infants with clinical RDS, avoiding unnecessary therapy, potential risks, and costs for those who would not benefit. Administration methods include endotracheal tube, intubation with rapid extubation, thin catheter, laryngeal mask, hypopharyngeal deposition, and, more recently, aerosolized or nebulized approaches, though the effectiveness of the latter remains unproven. For this review, a prophylactic strategy refers to intubation and bolus surfactant administration immediately after birth, while selective therapy refers to administration once evidence of RDS is present. The effect of surfactant may differ in infants stabilized early on continuous positive airway pressure (CPAP) and those whose mothers received a complete course of antenatal corticosteroids. In these infants, the benefits of prophylactic surfactant appear less pronounced than in neonates who did not receive early CPAP or antenatal steroids. In this update, we explored these factors in subgroup analyses, as in the previous version of the review. Additionally, we examined how the threshold of FiO₂ (fraction of inspired oxygen) used to initiate selective treatment, as well as the method of surfactant administration, might influence the effect of the surfactant replacement strategies. OBJECTIVES: To compare the effect of prophylactic surfactant administration versus selective surfactant administration on morbidity and mortality in preterm infants at risk of respiratory distress syndrome (RDS). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and CINAHL on 31 January 2025. To identify any studies not captured by our search of bibliographical databases, we also searched clinical trial registers, conference proceedings, and reference lists of included studies and surfactant reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs comparing the effects of prophylactic surfactant administration in preterm infants at risk of RDS versus surfactant treatment of preterm infants with established RDS. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were mortality, neurodevelopmental disability, and complications of preterm birth including pneumothorax and chronic lung disease. We performed meta-analysis and expressed our results using mean difference (MD), standardized mean difference (SMD), or risk ratio (RR), with 95% confidence intervals (CIs). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We identified 10 relevant individually randomized controlled trials (involving 3151 preterm infants). All trials were conducted in North America and Europe. Eight were conducted in the 1990s, and two were published more recently, at a time of greater use of antenatal steroids and nasal continuous positive airway pressure (CPAP). Nine trials were at risk of performance and detection bias. When all studies are considered, prophylactic surfactant probably results in little to no difference in the risk of chronic lung disease (CLD) at 36 weeks' postmenstrual age compared to selective use of surfactant (RR 1.13, 95% CI 1.00 to 1.28; I² = 0%; RD 0.04, 95% CI 0.00 to 0.08; NNTH 25 95% CI 13 to > 1000; I² = 0%; 5 trials, 1874 infants; moderate-certainty evidence). There may be little to no difference between the prophylactic and selective approaches in moderate to severe neurodevelopmental impairment (RR 0.83, 95% CI 0.57 to 1.21; 1 trial, 976 infants; I AUTHORS' CONCLUSIONS: Studies of prophylactic surfactant administration in infants at risk of developing RDS that were conducted prior to widespread use of maternal prenatal steroids and routine early stabilization on CPAP demonstrated a decreased risk of mortality and slight reduction in pneumothorax compared with selective surfactant use in infants with established RDS. However, larger trials that reflect current neonatal care practices do not support this finding. Instead, they show that, compared with selective surfactant administration in infants stabilized on CPAP, prophylactic surfactant likely results in little to no difference in the risk of chronic lung disease and slightly increases mortality.

BACKGROUND: MicroRNA-144 (miR-144) has been implicated in inflammation and glucocorticoid (GC) receptor regulation, but its role in GC sensitivity during acute respiratory distress syndrome (ARDS) is unclear. This study aimed to investigate the impact of miR-144 on GC therapeutic efficacy, elucidate its underlying molecular mechanisms in ARDS, and validate its clinical application value. METHODS: First, we established a sepsis-induced ARDS rat model with five groups (n = 6 each): control, model, GC, GC + miR-144 mimic, or GC + miR-144 inhibitor. Body weight, inflammatory markers, lung wet/dry ratio, histopathology, and miR-144/GRα/GRβ/NF-κB mRNA were assessed after the 5-day treatment. Second, we prospectively enrolled 63 ARDS patients receiving methylprednisolone and classified them as GC-sensitive (n = 43) or GC-resistant (n = 20) based on clinical outcomes. The correlations of baseline miR-144, GRα, GRβ, and NF-κB mRNA levels in patient blood were analyzed, and the predictive value of miR-144 for GC sensitivity was evaluated. RESULTS: In rats, miR-144 inhibitor enhanced GC efficacy (improved body weight recovery, reduced lung edema and inflammation), while mimic attenuated these effects. Mechanistically, in rat lung tissue, sepsis stimulation increased miR-144, GRβ, and NF-κB while reducing GRα expression; GC reversed these changes; miR-144 inhibitor further reduced GRβ/NF-κB, whereas mimic antagonized this without affecting GRα. In patients, GC-resistant individuals showed significantly higher miR-144, GRβ, and NF-κB levels than sensitive ones. Strong positive correlations were observed between miR-144 and both GRβ and NF-κB, and miR-144 effectively predicted GC resistance in ARDS. CONCLUSIONS: MiR-144 regulates GC sensitivity via the GRβ/NF-κB axis in ARDS. Baseline miR-144 level is a promising biomarker for predicting GC response, providing a basis for individualized treatment.

INTRODUCTION: Interleukin-17A (IL-17A) signalling disrupts fibrinolysis and drives inflammation and fibrotic remodelling in acute lung injury (ALI). IL-17A signals through a heterodimeric complex of IL-17RA and IL-17RC, initiating a cascade of immunological responses, including the synthesis of chemokines and inflammatory mediators. This leads to compromised epithelial integrity and barrier dysfunction. To determine the therapeutic potential of IL-17RA and IL-17RC neutralising antibodies on inflammation and the fibrinolytic system in a bleomycin (BLM)-induced ALI model. METHODS: A549 cells and C57BL/6 mice were used to study the effects of neutralising IL-17RA and IL-17RC. ALI was induced in both models using BLM. A549 cells were subsequently treated with IL-17RA and IL-17RC neutralising antibodies. In mice, ALI was induced via intranasal administration of BLM. Neutralising antibodies against IL-17RA and IL-17RC were administered intranasally. Collected lung tissues and cell pellets were assessed for expression of the fibrinolytic system and inflammation. RESULTS: Our study demonstrates the active involvement of IL-17 receptors, IL-17RA, and IL17RC in ALI. BLM treatment significantly increased PAI-1 expression ~ 3.5-fold, whereas neutralisation of IL-17RA or IL-17RC markedly reduced PAI-1 levels by over 90% compared to the BLM treated group, while restoring the expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) and suppressing pro-inflammatory cytokines TNF-α and IL-6. DISCUSSION: This study reveals that neutralisation of IL-17RA or IL-17RC in BLM-induced ALI reduced inflammation and restored normal fibrinolytic balance. CONCLUSION: Our study suggests that IL-17RA and IL-17RC play a major role in inflammation and the regulation of fibrinolysis during ALI. Targeting these receptors can mitigate lung injury and restore normal fibrinolytic activity, highlighting a novel receptor-specific IL-17 blockade as a potential therapeutic strategy to limit lung injury and improve ALI and Acute respiratory distress syndrome (ARDS) outcomes.